Azoospermia is determined when no spermatozoa can be detected on high-powered microscopic examination of a pellet after centrifugation of the seminal fluid. A physician can initially identify the causes of azoospermia by an exhausted history and a complete physical examination. Men with testicular or pretesticular azoospermia should be offered genetic testing and measurement of serum sex hormones to exclude genetic abnormalities or hypogonadism. And the CFTR mutation test should be recommended to exclude the possibility of CF present in the offspring when azoospermia is related to CBAVD or primary epididymal obstruction. Testicular size, inhibin B levels and serum FSH concentration help to evaluate spermatogenesis of the testis, and diagnostic testicular biopsy can further distinguish obstructive causes from testicular failure in case of normal-sized testes. Vasography may be used to identify the site of obstruction, but only when reconstructive surgery is performed.
Azoospermia ; diagnosis ; etiology ; Humans ; Male ; Testis ; pathology

OBJECTIVETo investigate the value and clinical application of the Three-Step Sperm Retrieval method in improving the sperm retrieval rate for non-obstructive azoospermia (NOA) patients.

METHODSSeventy-three NOA patients underwent Three-Step Sperm Retrieval in the following order of procedures: testicular fine needle aspiration (TFNA), testicular sperm extraction (TSE), and microdissection testicular sperm extraction (MD-TSE). The testicular tissue obtained from each step was observed for spermatozoa under the 400-fold inverted microscope. If spermatozoa were found in one step, the operation would be stopped; otherwise, the next step would be carried out. The testicular tissue was subjected to pathological examination.

RESULTSSpermatozoa was found in the testicular tissue in 38.4% of the cases (28/73) at TFNA as the first step, in 52.1% (38/73) at TFNA and TSE, and in 64.4% (47/73) at TFNA, TSE and MD-TSE. Pathological examination showed 25 of the cases to be Sertoli cell-only syndrome, 21 to be sperm maturation arrest and the other 27 to be hypospermatogenesis, in which spermatozoa were found in 10, 14 and 23 cases, respectively.

CONCLUSIONThe Three-Step Sperm Retrieval method can significantly improve the sperm retrieval rate for NOA patients. And the sperm retrieval rate is associated with the pathological type of the testicular tissue, a higher rate with hypospermatogenesis.

Adult ; Azoospermia ; Humans ; Male ; Sperm Retrieval ; Testis ; pathology ; surgery

OBJECTIVETo study the relationship between the testis volume and types of spermatogenic cells derived from testicular biopsy in patients with azoospermia or cryptozoospermia.

METHODSWe collected testicular pathological biopsies from 492 infertile patients with azoospermia or cryptozoospermia reported in our hospital, classified them according to the testicular histological classification methods in WHO Manual for Standardized Investigation, Diagnosis and Management of the Infertile Male, and analyzed the relationship of the testis volume with the results of semen analyses and testicular histology.

RESULTSOf the 492 cases, 90.5% (445/492) were azoospermia and 9.5% (47/492) cryptozoospermia; mature spermatozoa were present in the seminiferous tubules in 17.9% (88/492) but absent in 42.9% (211/492), and Sertoli cell-only syndrome indicated in 39.2% (193/492); the testis volume was < or = 10 ml in 38.6% (190/492) and < or = 5 ml in 7.9% (39/492). Cryptozoospermia was detected in 14.8% (13/88) of those with mature spermatozoa in the seminiferous tubules, in 11.4% (24/211) of those without, and in 5.2% (10/193) of those with Sertoli cell-only syndrome, with a significantly lower rate in the latter group than in the former two (P < 0.05).

CONCLUSIONSpermatogenesis of the testis may be focal and difficult to be completely reflected by a single testicular biopsy, and it may exist even if the testis volume is significantly below the reference value. The indications for testicular biopsy should not be improperly expanded. The WHO testicular histological classification methods have provided a convenient and effective guidance for further clinical examinations and establishment of a protocol.

Adult ; Azoospermia ; pathology ; Biopsy ; Humans ; Male ; Middle Aged ; Semen Analysis ; Spermatogenesis ; Spermatozoa ; pathology ; Testis ; pathology

Patients with non-obstructive azoospermia was once considered to be infertile due to impaired testicular spermatogenesis and consequent absence of sperm in the ejaculate. With the advent of intracytoplasmic sperm injection (ICSI), various testicular sperm retrieval techniques have been introduced recently, including fine needle aspiration, testicular sperm extraction, microdissection testicular sperm extraction, and so on. A large number of studies show that sperm can be retrieved in non-obstructive azoospermia patients, even in those with Klinefelter syndrome, because of the existence of isolated regions of spermatogenic tissue within the testis. 2010 EAU guidelines on male infertility recommend testicular sperm extraction or microdissection testicular sperm extraction for sperm retrieval from non-obstructive azoospermia. However, compared with testicular sperm extraction, the latter has a higher sperm retrieval rate with minimal postoperative complications. This article presents an overview on the prediction, operative procedure, sperm retrieval rate and postoperative complications of microdissection testicular sperm extraction.
Azoospermia ; pathology ; Humans ; Klinefelter Syndrome ; pathology ; Male ; Microdissection ; Sperm Retrieval ; Spermatozoa ; Testis ; pathology

OBJECTIVETo evaluate the correlation of neutral alpha-glucosidase in seminal plasma with the location of epididymal obstruction in azoospermia men.

METHODSWe detected neutral alpha-glucosidase activity in the seminal plasma of 59 men with obstructive azoospermia followed by determining the location of epididymal obstruction by scrotal exploratory surgery. Then we analyzed the correlation between neutral alpha-glucosidase and the location of epididymal obstructive azoospermia.

RESULTSAmong the total number of patients, there were 25 cases of bilateral cauda epididymal obstruction, 15 bilateral corpus, 12 bilateral caput, 4 unilateral caput-opposite cauda, and 3 unilateral corpus-opposite cauda. The neutral alpha-glucosidase levels in the seminal plasma of bilateral cauda, corpus and capus epididymal obstructions were (4.1 +/- 1.9), (13.8 +/- 4.4) and (46.8 +/- 19.3) mU per ejaculate, respectively, with statistically significant differences among the three groups (P < 0.05).

CONCLUSIONNeutral alpha-glucosidase activity is significantly correlated with the location of epididymal obstruction in azoospermia men, which helps to locate epididymal obstruction, evaluate surgical prognosis and reduce the time of scrotal exploratory surgery.

Adult ; Azoospermia ; enzymology ; pathology ; Epididymis ; pathology ; surgery ; Humans ; Male ; Semen ; enzymology ; alpha-Glucosidases ; metabolism

OBJECTIVETo evaluate histopathologic examination of the testis tissue from testicular sperm aspiration (TESA).

METHODSWe analyzed the results of inverted microscopy and histopathologic examination of 96 samples of testis tissue from TESA, and compared the accuracy of the two methods in detecting sperm in the testis tissue.

RESULTSAmong the 11 cases in which sperm was found by inverted microscopy, 9 were confirmed by histopathologic examination, and among the 57 cases in which sperm was not detected by inverted microscopy, 11 (19.3%) were found with sperm by histopathologic examination. Histopathologically, the cases in which sperm was not found by inverted microscopy included Sertoli-cell-only syndrome (n = 34), maturation arrest (n = 12) and hypospermatogenesis (n = 11).

CONCLUSIONHistopathologic examination may reveal sperm in the TESA testis tissue proved to be sperm-absent by microscopy, and thus offer valuable information for a second testicular sperm retrieval.

Adult ; Azoospermia ; pathology ; Humans ; Male ; Middle Aged ; Sperm Count ; Sperm Retrieval ; Testis ; pathology ; Young Adult

OBJECTIVETo investigate the expression of inhibin B betaB subunits in human testicular tissues.

METHODSEighty-three cases of the azoospermia underwent testicular biopsy. In accordance with the pathological alterations of spermatogenesis, the samples were divided into four groups: Sertoli-cell-only syndrome (n = 21); hypospermatogenesis (n = 20), maturation arrest (n = 24) and almost normal spermatogenesis (n = 18). Immunohistochemical staining for inhibin B betaB subunits was conducted on the paraffin-embedded sections of different spermatogenesis to localize inhibin B betaB subunits in the seminiferous tubules.

RESULTSImmunohistochemically, positive products of inhibin B betaB subunits were found in both the seminiferous tubules and interstitial tissues of the testis as brown or yellow particles in the cytoplasm. Leydig cells and early intermediate spermatogenic cells showed a very strong positivity; Sertoli cells in the seminiferous tubules were mostly positive; peritubular myoid cells showed a weak positive staining; but no positive expression of inhibin B betaB subunits was found in late spermatids and mature sperm.

CONCLUSIONInhibin B may be produced by both Sertoli cells and early spermatogenic cells in the seminiferous tubules.

Adult ; Azoospermia ; metabolism ; pathology ; Humans ; Immunohistochemistry ; Inhibin-beta Subunits ; biosynthesis ; Male ; Testis ; metabolism ; pathology

OBJECTIVETo investigate the expression of corticosteroids and regional expression 16 (CR16) in the testis of patients with idiopathic azoospermia and the role of CR16 in spermatogenesis.

METHODSImmunohistochemistry and RT-PCR were used to detect the expression levels of the CR16 protein and mRNA in the testes of 48 patients with idiopathic azoospermia and 10 healthy men.

RESULTSImmunohistochemistry showed that the CR16 protein expressed in the Sertoli cells and spermatids-binding region in the epithelium of seminiferous tubules. The level of the CR16 protein was markedly lower in the idiopathic azoospermia patients than in the healthy men, and RT-PCR also showed a significantly decreased level of CR16 mRNA in the testis of the patients.

CONCLUSIONThe expressions of the CR16 protein and mRNA decrease markedly in the testis of patients with idiopathic azoospermia, indicating a correlation with the pathogenesis of azoospermia.

Adult ; Azoospermia ; metabolism ; pathology ; Case-Control Studies ; Cytoskeletal Proteins ; metabolism ; Humans ; Male ; Testis ; metabolism ; pathology

OBJECTIVETo primarily study the influence of recombination abnormality in human spermatocyte meiosis on the pathology of the patients with non-obstructive azoospermia (NOA).

METHODSWe obtained testis tissues from 6 NOA patients by testicular biopsy and divided the tissue of each patient into 2 portions, one for pathological examination and the other for immunofluorescent staining. We observed the synaptonemal complex and the numbers of the recombination sites on homologous chromosomes, and analyzed the relationship between abnormal recombination and pathological findings.

RESULTSPathological examination showed that the basement membrane of the seminiferous tubules was thickened in 3 of the cases and atrophied in the other 3, the number of autosomal MLH1 foci in a spermatocyte ranging from 10 to 50 in the former 3, and from 30 to 50 in the latter 3.

CONCLUSIONThe increased range of the homologous chromosomal recombination frequency may be one of the possible factors for the thickening of seminiferous tubule basement membrane and even lumen occlusion in NOA patients.

Adult ; Azoospermia ; genetics ; pathology ; Chromosome Aberrations ; Humans ; Male ; Meiosis ; Recombination, Genetic ; Spermatocytes ; cytology ; Young Adult

Nonobstructive azoospermia (NOA) is a severe condition in infertile men, and increasing numbers of causative genes have been identified during the last few decades. Although certain causative genes can explain the presence of NOA in some patients, a proportion of NOA patients remain to be addressed. This study aimed to investigate potential high-risk genes associated with spermatogenesis in idiopathic NOA patients by whole-exome sequencing. Whole-exome sequencing was performed in 46 male patients diagnosed with NOA. First, screening was performed for 119 genes known to be related to male infertility. Next, further screening was performed to determine potential high-risk causative genes for NOA by comparisons with 68 healthy male controls. Finally, risk genes with high/specific expression in the testes were selected and their expression fluctuations during spermatogenesis were graphed. The frequency of cystic fibrosis transmembrane conductance regulator (CFTR) gene pathogenic variant carriers was higher in the NOA patients compared with the healthy controls. Potential risk genes that may be causes of NOA were identified, including seven genes that were highly/specifically expressed in the testes. Four risk genes previously reported to be involved in spermatogenesis (MutS homolog 5 [MSH5], cilia- and flagella-associated protein 54 [CFAP54], MAP7 domain containing 3 [MAP7D3], and coiled-coil domain containing 33 [CCDC33]) and three novel risk genes (coiled-coil domain containing 168 [CCDC168], chromosome 16 open reading frame 96 [C16orf96], and serine protease 48 [PRSS48]) were identified to be highly or specifically expressed in the testes and significantly different in the 46 NOA patients compared with 68 healthy controls. This study on clinical NOA patients provides further evidence for the four previously reported risk genes. The present findings pave the way for further functional investigations and provide candidate risk genes for genetic diagnosis of NOA.
Humans ; Male ; Azoospermia/pathology* ; East Asian People ; Exome Sequencing ; Mutation ; Proteins/genetics*